Role of Hyperbaric Oxygen Therapy in the Treatment of Foot Ulcers - Literature review Example

Role of Hyperbaric Oxygen Therapy in the Treatment of Foot Ulcers Introduction Therapeutic application of oxygen under high pressure is known ashyperbaric oxygen therapy (HBOT). Exhaustive studies in both animals and human beings over the past 2 decades have found several applications of HBOT, some of which include burns, acute traumatic wounds, gas gangrene, crush injury, chronic non-healing wounds, late sequelae of radiation injury and compartment syndrome (Sahni, 2004). As far as non-healing ulcers in the foot are concerned, there is enormous evidence to suggest application of HBOT. In this research essay, the role of HBOT in the management of non-healing foot ulcers will be evaluated through review of literature and critical analysis. Aims The main aim of this study is to evaluate the benefits of HBOT in the management of non-healing foot ulcer. Background and rationale Wound in lower limb are common and have tendency to turn chronic. There are basically 3 types of ulcers which can present in the lower limb. They are venous stasis ulcers, arterial or ischemic ulcers and neuropathic or diabetic ulcers. It is important to identify the type of wound because management and prognosis are different for different types of wound. Venous stasis ulcers are mainly located below the knee and in the inner aspects of the leg just above the ankle, like the medial malleolus (Gabriel and Camp, 2008). They occur when inadequate action of the calf muscle to pump out blood results in venous hypertension (Gabriel and Camp, 2008). The base of the ulcer is usually red, the borders are irregular and the ulcer may be covered with yellowish tissue. Fluid drainage is a characteristic feature of venous ulcer. The surrounding skin will be discolored and swollen and may feel warm (Gabriel and Camp, 2008). Ischemic or arterial ulcers are usually located in the feet, especially in regions where there is friction between toes or parts of feet with shoes, or when there is a deformity. They are more likely to occur in the periphery where there is decreased blood supply. The ulcer base is yellowish, grey or black and does not bleed (Gabriel and Camp, 2008). The borders are initially irregular and later have a regular appearance. Neuropathic ulcers commonly occur in diabetic patients and they are usually located at pressure points on the plantar aspect of the feet. Neuropathy causes loss of foot sensation and also changes in sweat-producing glands increasing the risk of being unaware of foot trauma, injuries and callosities. The ulcers appear punched out with the surrounding skin callosed. The ulcer may appear pink or brown (Gabriel and Camp, 2008). Lower extremity ulcers have varied prognosis and are associated with many complications. They are the most common causes for limb amputation in diabetic population (Armstrong and Lavery, 1998). Hence it is important to manage them appropriately. Good management is possible through understanding of the principles of wound healing. Wound healing occurs either by primary healing or secondary healing. In chronic foot ulcers, the type of wound healing is healing by secondary intention in which the inflammatory response is more intense and larger quantities of granulomatous tissue is produced (Mercandetti and Cohen, 2008). There are 3 distinct phases of wound healing and they are inflammatory phase, proliferative phase and remodelling phase. In inflammatory phase, hemostasis and inflammation occur. This phase is followed by proliferative phase that begins 3-4 days after onset of inflammatory phase. In the proliferative phase, fibroplasia, deposition of the matrix, angiogenesis and re-epithelialization occur. In chronic ulcers, these subphases do not occur in a smooth manner due to various reasons like lack of proper nutrition, persistence of pressure and inadequate blood supply (Mercandetti and Cohen, 2008). HBOT, increases the oxygenation of the wound bed and facilitates formation of the matrix. This enhances angiogenesis and development of microvascular circulation. This further enhances supply of nutrition and removal of toxins from the wound, which are critical for wound healing. The main reason for therapeutic benefits of HBOT is the ability of the tissues to receive pharmacological doses of oxygen essential to heal tissues, which is otherwise not possible through oxygen in room air or 100 percent oxygen delivered at room pressures. When administered for the purpose of wound management, each treatment dive consists of administering 100 percent oxygen for 90 minutes at 45 feet of sea water. This is equivalent to 2.36 atmospheres of 100 percent oxygen (Sahni, 2004). The oxygen is delivered through specialised equipment known as hyperbaric chamber which can be monoplace or multiplace. The oxygenation of tissues is 11 times the normal value and this occurs because of diffusion gradient and pressure effects of oxygen (Sahni, 2004). Hyperoxygenation of the tissues triggers angiogenesis and increased microcirculation in the ischemic tissue. It also upregulates antibacterial effects, leukocyte effects and growth regulation factors and down regulated inflammatory cytokines, contributing to enhanced healing (Sahni, 2004). HBOT, like any other therapy, is associated with some side effects like sinus barotrauma, ear drum barotrauma, pulmonary barotrauma, myopia, precipitation of congestive heart failure and grand mal seizures (Sahni, 2004). Thus, during administration of this therapy the benefits must be weighed against side effects. HBOT is administered adjunct to standard wound therapy which is crucial to maintain healing environment of the chronic wound. Standard wound management in any foot ulcer is based on the site and cause of the wound and involves management of both systemic and local factors. Methodology The commencement of search in electronic databases was based on the inclusion/exclusion criteria and knowledge of the hierarchies of evidence. The databases which were used for retrieval of articles were PubMed, Medline search and Google Scholar. The terms used for search were "foot ulcers" and "hyperbaric oxygen therapy" or "HBOT". Each search yielded several articles. Nine articles were retrieved for the literature review will be be analyzed below. Literature review and critical analysis Theoretically, it is known that hyperbaric oxygen therapy increases the oxygen content in the tissues and facilitates healing. Practically several studies have observed, examined and experimented this therapy for the purpose of wound healing. In this literature review, impact of this therapy adjunct to healing of chronic foot wounds is done and critically evaluated. Londahl et al (2010) conducted a randomized controlled and double blinded trial to compare and evaluate the outcomes of HBOT in patients with chronic diabetic foot ulcers in comparison with patients with similar wounds and receiving hyperbaric air. The patients in both the groups received hyperbaric therapy for eight weeks, five days a week in an ambulatory setting. This article demonstrated that HBOT is an useful adjunct to standard treatment and facilitates wound healing. In a systematic review by Kranke et al (2004), 5 major randomized controlled trials were reviewed to ascertain the implications of hyperbaric wound therapy on chronic wounds. Four of these were evaluated for diabetic foot ulcer, involving a total of 147 patients. Pooled data from 3 of these trials and consisting of 118 participants demonstrated decrease in the risk of major amputation when HBOT was administered adjunct to standard wound therapy as against those who receive only normal wound care (RR- 0.31, 95% CI -0.13 to 0.71). According to this analysis treating four patients with HBOT prevents one amputation (NNT -4, 95%- CI 3 to 11). In the other two trials which included 48 patients, minor amputation rate was studied. From those studies, it was evidenced that HBOT does not decrease the risk of minor amputation. In one study, the rate of healing was studied and HBOT showed improvement after one year of treatment (RR for failure to heal with sham 2.3, 95%CI 1.1 to 4.7, P=0.03). In yet another study on venous ulcers, reduction of wound size was noted at 6 wks. No studies pertaining to pressure ulcers and arterial ulcers were suitable for the systematic review. The researchers of this systematic review concluded that diabetes-related foot ulcers were benefited with HBOT because it not only decreased the risk of major amputation, but also improved chances of healing at one year. This study mainly evaluated foot ulcers and the benefits were found only in diabetic ulcers, not in venous or arterial ulcers. Also, it only decreased the risk of major amputation and not minor amputation. Thus, it implies that the benefits of HBOT are limited only to foot ulcers with diabetes etiology and that too only to decrease the risk of major amputation. Similar reports were provided by another systematic study by Roeckl-Wiedmann et al. In this study too only randomised controlled trials pertaining to foot ulcers were located. Data was gathered from six trials. Five trials in this study reported about diabetic ulcers. Data from these indicated. that HBOT was significantly associated with risk of reduction of major amputation (RR: 0.31; C.I 0.13 to 0.71) However, there was no evidence to suggest reduction of risk with reference to minor amputation. One trial was done on venous ulcers and evidence from the study suggested that HBOT reduced the size of the wound at the end of treatment, but this improvement could not be seen on follow up. The review concluded that HBOT reduced the risk of major amputation in diabetic ulcers. The researchers opined that evidence pertaining to benefits in other types of ulcers is lacking and furthers trials are warranted in this regard. Even this study demonstrated the benefits of HBOT only in decreasing the risk of major amputation and not minor amputation. Implications of HBOT on other types of wound, was evaluated in yet another systematic review by Goldman (2009). In this study, the author reviewed 64 observational studies and randomized controlled trials to ascertain the role of HBOT on wound healing outcomes. In patients with diabetic foots ulcer with surgical complications, HBOT improved chances of healing (OR 9.992, 95% CI: 3.972-25.132) and decreased chances of amputation. In seven studies, measurement of hyperoxygenation was done using transcutaneous oximetry and evidence showed that HBOT hyperoxygenated at-risk tissue. One study associated HBOT with remission of 85 percent refractory osteomyelitis in the lower limb. This systematic review showed high evidence of association between HBOT and decreased risk of amputation in patients with diabetic foot ulcer. The review also found moderate evidence about promotion of wound healing in refractory osteomyelitis, calciphylactic and refractory vasculitic ulcers and arterial ulcers. With regard to benefits of HBOT on the "take" of grafts and flaps that are compromised low-to-moderate level of evidence was noted. This study reported implications of HBOT in not only decreasing the risk of major amputation, but also in decreasing minor amputation. Evidence, though not of high level was seen in the benefits of HBOT in managing other types of foot wounds too. With reference to implications on healing rate of the wound, a systematic review by Kessler et al (2003), in which the researchers conducted a randomized controlled trial to ascertain the benefits of systemic HBOT on the course of healing of diabetic foot ulcers that are chronic can be evaluated. Patients whose ulcers did not heal for 3 months of time were included in the study. HBOT was administered for 5 days a week for 2 weeks, with each session lasting for 90 minutes. The main outcome that was measured was the size of the ulcer of the foot that was ascertained a day before HBO and at the end of treatment using computer tracing graphics. This study demonstrated a rise in transcutaneous oxygen pressure from 21.9mmHg to 454 mmHg. On day-15 of therapy, significant reduction in the size of the wound was demonstrated (41.8 +/- 25.5 vs. 21.7 +/- 16.9% in the control group [P = 0.037]). From the results of the study, the researchers concluded that administration of HBOT as an adjunct to standard multidisciplinary management of nonischemic diabetic foot ulcers doubles the healing rate of the wound. All these studies have been done on chronic foot ulcers and curiosity may arise to ascertain the role of HBOT in treating acute wounds of foot like crush injuries or surgical ounds, so that they dont go through a chronic course. Eskes et al (2010) conducted a systematic review of randomized controlled trials to ascertain the effects of HBOT on the healing of acute wounds. One major trial reported better uptake of skin graft when HBOT was administered (95% healthy graft area risk ratio (RR) 3.50; 95% confidence interval (CI) 1.35 to 9.11). Another trial reported better healing of crush injuries with HBOT (RR 1.70; 95% CI 1.11 to 2.61). In yet another trial, HBOT therpy demonstrated better graft uptake than with dexamethasone or heparin therapy. Thus implications for management of acute foot wounds also has been ascertained in this study. Another study also demonstrated similar reports. In a prospective study by Kalani et al (2002), 38 patients with diabetic foot ulcers were evaluated with respect to their transcutaneous oxygen tension, HbA1c and peripheral blood pressure. 17 patients underwent underwent HBOT. 76 percent of these patients, who were followed up for a period of 3 years had intact skin healing. From the results of the study, it was evident that adjunctive HBOT helped in healing of chronic ulcers with tissue hypoxia. It reduced amputation risk, accelerated healing rate and enhanced complete healing chances. The researchers recommended further researchers to ascertain the role of HBOT in the management of acute wounds. In a retrospective controlled study by Albuquerque E Sousa (2005), the benefits of HBOT administered systemically, on patients with diabetes and chronic wound lesions in lower limbs was evaluated. 96 patients were studied, of which 55 patients received HBOT. The treatment was administered using multiplace hyperbaric oxygen chamber for 90 minutes, at 2.5 absolute atmospheres once a day for 5 days a week. Both the study and control groups were followed up several weeks. From the data analysis and results of the study, it was evident that HBOT increased the mean healing time by 13 times and decreased the need for amputation by atleast 2 times. The researchers opined that increase in microvascular blood supply secondary to increased fibroblast collagen production was the main cause for benefits in HBOT. Hyperbaric therapy increases tissue oxygenation levels which are determined by the dosing of oxygen administered. Thus, it is important to know whether increased doses cause better healing. Chen et al conducted a study evaluating the effectiveness of HBOT in treating infected diabetic foot ulcers. 44 patients were recruited into the study and randomly assigned into two groups. While in one group, less than 10 sessions of HBOT were administered, the other group received more than 10 sessions. In the first group, feet preservation was achieved in 33.3 percent patients and in the second group, feet preservation was achieved in 78.3 percent. The researchers concluded that HBOT accelerated wound healing and helped in restoration of tissue. The beneficial effect was dose dependent, i.e higher the dose of HBOT received, greater was the healing rate. This literature review included three randomised controlled trials, one prospective study, one retrospective and four systematic review. Most of the data in these studies is related to diabetic ulcers in the foot. Thus, naturally, implications for diabetic foot ulcers can be deduced in these studies. While most of the studies favour fast healing and decreased risk of major amputation, it is unclear as to why minor amputation risk is not decreased. Also some studies show improvement of healing rates in the initial stages and no change with treatment in the long run. Considering the cost and the clumsiness of application, it is yet uncertain whether HBOT, though has definite benefits on chronic leg diabetic ulcers can be recommended as adjunct therapy. Also the data in this review regarding other types of ulcers is minimal to ascertain the role of HBOT in the management of other leg ulcers. Conclusion HBOT is administration of 100 percent oxygen at high pressures so that the tissue oxygen levels rise and help in the development of matrix and angiogenesis, thus enhancing nutrition and metabolism of the wound bed. Implications of HBOT on foot ulcers is important because ulcers in the lower limb are nasty healers, especially in patients with diabetes. This literature review has identified the role of HBOT in improving healing and decreasing the risk of major amputation in diabetic foot ulcers. However, the benefits of this therapy cannot out weigh the costs associated because, the risk of minor amputation and healing on long term follow up is uncertain. Also, there is not much evidence to suggest the benefits of this therapy on other types of foot ulcers like ischemic ulcers and venous ulcers. References Albuquerque E Sousa, J. (2005). [Long-term evaluation of chronic diabetic foot ulcers, non-healed after hyperbaric oxygen therapy]. Rev Port Cir Cardiotorac Vasc., 12(4), 227-37. Armstrong, D.G., and Lavery, L.A. (1998). Diabetic Foot Ulcers: Prevention, Diagnosis and Classification. American Family Physician. Retrieved on 14th November from http://www.aafp.org/afp/980315ap/armstron.html Benton, D.C. and Cormack, D.F.S. (2000). Reviewing and evaluating the literature: In: Cormack, D.F.S. (Ed.). The Research Process in Nursing. 4th Edition. Oxford: Blackwell Publishers Limited, 103 – 113. Chen, C.E., Ko, J.Y., Fong, C.Y., Juhnm R.J. (2010). Treatment of diabetic foot infection with hyperbaric oxygen therapy. Foot Ankle Surg., 16(2), 91-5. Eskes, A., Ubbink, D.T., Lubbers, M., Lucas, C., Vermeulen, H. (2010). Hyperbaric oxygen therapy for treating acute surgical and traumatic wounds. Cochrane Database Syst Rev., 6, 10:CD008059. Evans, D. (2003). Hierarchy of evidence: a framework for ranking evidence evaluating healthcare interventions. Journal of Clinical Nursing, 12(1), p. 77 – 84. Gabriel, A., and Camp, C.C. (2008). Vascular Ulcers. Emedicine from WebMD. Retrieved on 14th November from http://emedicine.medscape.com/article/1298345-overview Goldman, R.J. (2009). Hyperbaric oxygen therapy for wound healing and limb salvage: a systematic review. PM R, 1(5), 471-89. Kalani, M., Jörneskog, G., Naderi, N., Lind, F., and Brismar, K. (2002). Hyperbaric oxygen (HBO) therapy in treatment of diabetic foot ulcers. Long-term follow-up. J Diabetes Complications, 16(2), 153-8. Kessler, L., Bilbault, P., Ortéga, F. (2003). Hyperbaric oxygenation accelerates the healing rate of nonischemic chronic diabetic foot ulcers: a prospective randomized study. Diabetes Care, (8), 2378-82. Kranke, P., Bennett, M., Roeckl-Wiedmann, I., and Debus, S. (2004). Hyperbaric oxygen therapy for chronic wounds. Cochrane Database Syst Rev., 2, CD004123. Kunimoto, B.T. (2001). Discussion of a Literature-Guided Approach. Ostomy/Wound Management, 47(5), 38–53. Lebel, D., Gortzak, Y., Nyska, M., Katz, T., Atar, D., and Etzion, Y. (2007). [Hyperbaric oxygen therapy for chronic diabetic wounds of the lower limbs--a review of the literature]. Harefuah., 146(3), 223-7, 244-5. Löndahl, M., Katzman, P., Nilsson, A., Hammarlund, C. (2010). Hyperbaric oxygen therapy facilitates healing of chronic foot ulcers in patients with diabetes. Diabetes Care, 33(5), 998-1003. Mercandetti, M., and Cohen, A.J. (2008). Wound Healing, Healing and Repair. Emedicine from WebMD. Retrieved on 14th November from http://emedicine.medscape.com/article/1298129-overview Roeckl-Wiedmann, I., Bennett, M., Kranke, P. (2005). Systematic review of hyperbaric oxygen in the management of chronic wounds. Br J Surg., 92(1), 24-32. Sahni, T., Hukku, S., Jain, M., et al. (2004). Recent Advances in Hyperbaric Oxygen Therapy. 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